In two-stage skin carcinogenesis, a carcinogen such as DMBA is applied to the skin at a level insufficient to produce tumors. Croton oil, a promoting agent, is applied which induces intense hyperplasia of the skin followed by the appearance of tumors of the skin. The mechanism by which croton oil promotes tumor formation is unknown but promotion is not simply the result of irritation or hyperplasia. In initiation-promotion the promoting agent amplifies the tumor cells while inhibiting or not affecting the normal cells. Our investigations of this system have indicated that cyclic AMP or DPE blocking agents will markedly inhibit promotion by croton oil or TPA. Similarly dexamethasone which is an effective PDE blocking agent also inhibits promotion. These agents are known to also affect the immune response. We have demonstrated that antibodies directed against normal tissues will inhibit normal cells in cell culture but will produce a pronounced enhancement of growth of transformed cells arising from the normal cells. The hypothesis of the proposed investigation is that croton oil induces autoantibodies to skin. These antibodies stimulate the tumor cells but inhibit or have little effect on the normal epidermis. It is proposed to test this hypothesis by: 1) Examining croton oil treated animals for autoantibodies to skin extracts, 2) measure the promoting effect of passive antibody to syngeneic skin in mice painted with DMBA, 3) measure the promoting effect of active immunity to allogeneic and syngeneic skin in mice painted with DMBA, 4) determine the effect of skin antibodies on transformed (DMBA) and primary cultures of skin.